1. Field of the Invention
This invention relates to new pharmaceutical compositions and methods for their preparation, and in particular it relates to taste-masked liquid compositions comprising a solution of a histamine H2-antagonist complexed with an alginate.
2. Description of Related Art
The histamine H2-receptor antagonists are a highly successful class of drugs. These compounds are widely prescribed to treat gastrointestinal disorders and are usually administered orally. Unfortunately, most members of this class have the drawback of having an extremely disagreeable taste. The art has recognized this problem and has applied many different approaches to trying to solve this problem.
U.S. Pat. No. 4,996,222 describes a pharmaceutical suspension of cimetidine having a pH of at least 7 wherein substantially all of the cimetidine is in the polymorph B crystalline form. The composition will contain a suspending agent. The composition may contain alginate as a thickening agent. Examples of suspending agents include xanthan gum, hydroxypropylmethylcellulose, methylcellulose, carageenan, sodium carboxymethyl cellulose, and sodium carboxymethyl cellulose/microcrystalline cellulose mixtures, particularly sodium carboxymethyl cellulose/microcrystalline cellulose mixtures.
Thus, in U.S. Pat. No. 5,576,344, a process for reducing the adverse taste and malodor associated with H2-receptor antagonist nizatidine is described. The process involves forming an aqueous solution of the compound and subjecting the solution to elevated temperatures sufficient for a period sufficient to cause a reduction in the adverse taste and/or malodor.
U.S. Pat. No. 5,622,980 describes a solid composition for oral administration of an H2-receptor antagonist which composition includes a silicate taste-masking agent capable of forming an adsorbate complex with the H2-antagonist wherein the complex exhibits a non-bitter taste. The complex inhibits the release of the H2-antagonist in the oral cavity.
Chewable tablets containing unpleasant tasting medicaments such as cimetidine are disclosed in U.S. Pat. No. 5,275,823. The palatability of the tablets is improved by including certain hygroscopic water-insoluble substances as extragranular excipients. Such excipients include cellulose derivatives, sodium starch glycolate and cross-linked polyvinylpyrrolidine.
A chewable dosage form containing a histamine H2-receptor antagonist in an amount which is effective to treat a gastrointestinal disorder is provided in a palatably acceptable form in U.S. Pat. No. 6,270,807. The dosage form comprises granules containing the histamine H2-receptor antagonist, which are provided with a taste-masking coating comprising a water-insoluble, water-permeable methacrylate ester copolymer in which the coating is applied to the granules in an amount which provides a taste-masking effect for a relatively short period during which the composition is being chewed by a patient, but which allows substantially immediate release of the histamine H2-receptor antagonist after the composition has been chewed and ingested.
U.S. Pat. No. 6,197,348 discloses a taste-masked pharmaceutical composition. There is provided a taste masked oral pharmaceutical composition including: a pharmaceutically active ingredient having a pH-dependent solubility; a polymer encapsulating said pharmaceutically active ingredient, said polymer having a quaternary ammonium functionality; a suspending medium for suspending the encapsulated pharmaceutically active ingredient, said medium adjusted to a predetermined pH at which the pharmaceutically active ingredient remains substantially insoluble; and wherein the pharmaceutically active ingredient is taste masked by the combination of the polymer and suspending medium.
Taste masked immediate release micromatrix powders are described in U.S. Pat. No. 6,153,220. Taste masked immediate release micromatrix powders can be formed by spray drying the drug and cationic copolymer whereas sustained release micromatrix powders can be formed by granulating controlled release powders, which can be made by spray drying the drug with a retarding polymer, with the cationic copolymer. These powders containing drugs with poor organoleptic properties can be incorporated into conventional oral dosage forms such as sprinkles, suspension, fast melt tablets, chewable tablets or effervescent tablets.